Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

BACKGROUND:The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. RESULTS:The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. CONCLUSIONS:Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. Video abstract

Histological confinement of transglutaminase-mediated nit sheath crosslinking is essential for proper oviposition and egg coating in the human head louse, Pediculus humanus capitis

Background Head louse females secrete liquid gel, which is mainly composed of the louse nit sheath protein 1 (LNSP1) and LNSP2, when they lay eggs. The gel is crosslinked by transglutaminase (TG) to form the nit sheath, which covers most of the egg except the top operculum area where breathing holes are located. Knowledge on the selective mechanism of nit sheath solidification to avoid uncontrolled crosslinking could lead to designing a novel method of louse control, but no information is available yet. Methods To elucidate the crosslinking mechanisms of nit sheath gel inside the reproductive system of head louse females, in situ hybridization in conjunction with microscopic observation of the oviposition process was conducted. Results Histochemical analysis revealed that LNSP1 and LNSP2 are expressed over the entire area of the accessory gland and uterus, whereas TG expression site is confined to a highly localized area around the opening of posterior oviduct. Detailed microscopic observations of oviposition process uncovered that a mature egg is positioned in the uterus after ovulation. Once aligned inside the uterus, the mature egg is redirected so that its operculum side is tightly held by the ventral end of the uterus being positioned toward the head again and its pointed bottom end being positioned toward the dorsal end of the uterus, which functions as a reservoir for the nit sheath gel. Conclusions Physical separation of the TG-mediated crosslinking site from the ventral end of the uterus is necessary to avoid uncontrolled crosslinking inside the uterus and to ensure selective crosslinking over only the lower part of egg without any unwanted crosslinking over the operculum during oviposition. Graphical Abstrac

Induction of IL-10-producing CD4(+)CD25(+ )T cells in animal model of collagen-induced arthritis by oral administration of type II collagen

Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4(+)CD25(+ )T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG(1 )and decreased serum IgG(2a )as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-β from mononuclear lymphocytes was increased in the tolerized animals, and CD4(+ )T cells isolated from tolerized mice did not respond with induction of IFN-γ when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4(+)CD25(+ )subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4(+)CD25(+ )T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect

Laparoscopy-assisted distal gastrectomy for gastric cancer after liver transplantation

A case report described a 72-year-old man with a history of a deceased-donor liver transplantation (due to hepatitis B-associated end-stage liver cirrhosis) performed in 1994. The patient was diagnosed with renal cell carcinoma and pulmonary metastasis in 1997 and was successfully treated with radiofrequency ablation and thoracoscopic superior segmentectomy. There was no evidence of newly diagnosed metastatic lesions or recurrence until the 19th post-operative month. Gastric cancer was identified by endoscopy during a routine follow-up examination; the pre-pyloric antral lesion measured 1.5 cm in size and was histologically well-differentiated and confined to the submucosal layers on endoscopic ultrasound. Laparoscopic gastrectomy and lymph node dissection (D1 + β) was successfully performed in March 2009, and the patient was discharged on the 5th post-operative day without complications. This suggests that laparoscopic surgery is one of the feasible methods for resection of gastric cancer in liver transplant patients

Atopic Dermatitis-Like Skin Lesions Reduced by Topical Application and Intraperitoneal Injection of Hirsutenone in NC/Nga Mice

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD